Sulfuric Acid → 4-Chloro-3-cyanobenzoic acid

HRID 1817172Notes

Reaction equation

HRID 1817172 reaction equation
S(=O)(=O)(O)O.N[C:7]1[CH:8]=[C:9]([CH:13]=[CH:14][C:15]=1[Cl:16])[C:10]([OH:12])=[O:11].N([O-])=O.[Na+].[Cu](C#N)[C:22]#[N:23].[C-]#N.[K+].C(=O)([O-])[O-].[K+].[K+]>C1C=CC=CC=1.O>[Cl:16][C:15]1[CH:14]=[CH:13][C:9]([C:10]([OH:12])=[O:11])=[CH:8][C:7]=1[C:22]#[N:23]

Participants

9

Reactant 6

HCID 1118Sulfuric AcidHCID 9032Potassium CyanideHCID 11430Potassium CarbonateHCID 760923-Amino-4-chlorobenzoic acidHCID 23668193Sodium NitriteHCID 178418260HCID 178418260, compound

Product 1

HCID 226446124-Chloro-3-cyanobenzoic acidYield 19.3%

Reagents, catalysts & solvents 2

HCID 241BenzeneSolventHCID 962WaterSolvent2×

Conditions

Temperature
0 °C

Procedure

To a stirred mixture of conc. sulfuric acid (60 mL) and water (95 mL) containing 3-amino-4-chlorobenzoic acid (10.0 g, 57.1 mmol) was added sodium nitrite (10.0 g, 145 mmol) at 0° C. The mixture was stirred at 0° C. for 2 hours, and added to a stirred mixture comprising a mixture of water (250 mL) and benzene (175 mL) containing copper cyanide (7.1 g, 79.3 mmol), potassium cyanide (21.7 g, 333 mmol), potassium carbonate (285 g, 2.06 mmol) at a temperature not higher than 15° C. The resulting mixture was heated under stirring at 80° C. for one hour, cooled to room temperature, stirred under ice-cooling, and filtered using Celite to collect insolubles. The insolubles were washed with benzene (100 mL) and ether (100 mL). The aqueous portion was taken out, and made to pH 2 by addition of conc. hydrochloric acid under stirring and ice-cooling. The aqueous portion was subjected to extraction with ether (200 mL×2), dried over anhydrous sodium sulfate, and placed under reduced pressure to distill the solvent off. The residue was repeatedly purified by silica gel column chromatography (ethyl acetate/hexane), to obtain 2.0 g (yield 19%) of the titled compound as a pale yellow crystalline product.

Workup

  1. additionadded to a stirred mixture comprising
  2. temperatureThe resulting mixture was heated
  3. stirringunder stirring at 80° C. for one hour
  4. temperaturecooled to room temperature
  5. stirringstirred under ice-
  6. temperaturecooling
  7. filtrationfiltered
  8. customto collect insolubles
  9. washThe insolubles were washed with benzene (100 mL) and ether (100 mL)
  10. additionmade to pH 2 by addition of conc. hydrochloric acid
  11. stirringunder stirring
  12. temperatureice-cooling
  13. extractionThe aqueous portion was subjected to extraction with ether (200 mL×2)
  14. dry with materialdried over anhydrous sodium sulfate
  15. distillationto distill the solvent off
  16. customThe residue was repeatedly purified by silica gel column chromatography (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-9cc7396b0f3049e6ac5049ad0be4f3c7
Source dataset
uspto-grants-2009_10
Patent number
US07598254B2

Reaction notes

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